Atsushi Takeshita

Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis

BackgroundHepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM). It is crucial to elucidate the prognostic clinicopathological factors.MethodsEighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis.ResultsThe overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra- and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictive factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrahepatic recurrence were noted. In the subgroup with synchronous CRCLM, the combination of surgery and adjuvant chemotherapy controlled intrahepatic recurrence and improved the prognosis significantly.ConclusionsOptimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.

Significance of chymase-dependent angiotensin II formation in the progression of human liver fibrosis

Aim:  Angiotensin II may contribute to liver fibrogenesis. In addition to angiotensin‐converting enzyme (ACE), chymase, which is expressed by mast cells, is also known to be an angiotensin II‐forming enzyme. However, it is unclear which of these two angiotensin II‐forming enzymes plays a more important role in liver cirrhosis progression. In the present study, the role of angiotensin II‐forming enzymes in the progression of liver cirrhosis was clarified.

Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats

Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide (LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.

An operative case of hepatic pseudolymphoma difficult to differentiate from primary hepatic marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

Hepatic pseudolymphoma (HPL) and primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are rare diseases and the differential diagnosis between these two entities is sometimes difficult. We herein report a 56-year-old Japanese woman who was pointed out to have a space occupying lesion in the left lateral segment of the liver. Hepatitis viral-associated antigen/antibody was negative and liver function tests including lactic dehydrogenase, peripheral blood count, tumor markers and soluble interleukin-2 receptor were all within normal limit. Imaging study using computed tomography and magnetic resonance imaging were not typical for hepatocellular carcinoma, cholangiocarcinoma, or other metastatic cancer. Fluorodeoxyglucose-positron emission tomography examination integrated with computed tomography scanning showed high standardized uptake value in the solitary lesion in the liver. Under a diagnosis of primary liver neoplasm, laparoscopic-assisted lateral segmentectomy was performed. Liver tumor of maximal 1.0 cm in diameter was consisted of aggregation of lymphocytes of predominantly B-cell, containing multiple lymphocyte follicles positive for CD10 and bcl-2, consistent with a diagnosis of HPL rather than MALT lymphoma, although a definitive differentiation was pending. The background liver showed non-alcoholic fatty liver disease/early non-alcoholic steatohepatitis. The patient is currently doing well with no sign of relapse 13 months after the surgery. Since the accurate diagnosis is difficult, laparoscopic approach would provide a reasonable procedure of diagnostic and therapeutic advantage with minimal invasiveness for patients. Considering that the real nature of this entity remains unclear, vigilant follow-up of patient is essential.

Adult onset Still's disease with hemophagocytic syndrome and severe liver dysfunction

We report the case of a 55-year-old Japanese woman with adult onset Stills disease in whom hemophagocytic syndrome and severe liver dysfunction developed. High serum levels of ferritin, macrophage colony stimulating factor and interferon-gamma, which imply the presence of hemophagocytic syndrome, were detected. It is known that hemophagocytic syndrome is associated with adult onset Stills disease. In our case, many markedly swollen Kupffer cells with phagocytized red blood cells were found in the liver, as well as macrophages in the bone marrow and spleen. Accordingly, we believe that severe liver dysfunction in this case may have been related to hypercytokinemia due to hemophagocytic syndrome.

Development of Fibrosis in Nonalcoholic Steatosis through Combination of a Synthetic Diet Rich in Disaccharide and Low-Dose Lipopolysaccharides in the Livers of Zucker (fa/fa) Rats

Nonalcoholic steatohepatitis (NASH) can develop into end-stage disease such as cryptogenic cirrhosis and hepatocellular carcinoma. Hence, it is important to understand the pathogenesis of NASH. In general, the “two-hit theory” has prevailed as a pathogenic mechanism of NASH. According to this theory, lipopolysaccharides (LPS) contained in normal portal blood are the “second hit,” but their role is not completely understood. Based on this theory, we evaluated the role of LPS in NASH pathogenesis. For the first hit to develop metabolic abnormalities, a synthetic diet rich in disaccharide (synthetic diet: 12.1 cal% disaccharide) was fed to Zucker (fa/fa) rats for 12 weeks. For the second hit, 100 µg/kg LPS was injected intraperitoneally once daily for 2 weeks. Synthetic diet-fed rats treated with LPS showed an increase in the triglyceride content and higher expression of profibrogenic mRNAs in the liver. Plasma alanine aminotransferase levels were significantly elevated using this protocol. Furthermore, histological examination demonstrated that this protocol induced mild hepatic fibrosis and focal necrosis in the livers of all rats. Synthetic diet-fed Zucker (fa/fa) rats treated with LPS could be useful for understanding the development of hepatic fibrosis in the two-hit theory.

Primary hepatic benign schwannoma.

Schwannoma is predominantly a benign neoplasm of the Schwann cells in the neural sheath of the peripheral nerves. Occurrence of schwannoma in parenchymatous organs, such as liver, is extremely rare. A 64-year-old man without neurofibromatosis was observed to have a space-occupying lesion of 23mm diameter in the liver during follow-up examination for a previously resected gastrointestinal stromal tumor (GIST) in the small intestine. He underwent lateral segmentectomy of the liver under a provisional diagnosis of hepatic metastatic recurrence of the GIST. Histological examination confirmed the diagnosis of a benign schwannoma, confirmed by characteristic pathological findings and positive immunoreactions with the neurogenic marker S-100 protein, but negative for c-kit, or CD34. The tumor was the smallest among the reported cases. When the primary hepatic schwannoma is small in size, preoperative clinical diagnosis is difficult. Therefore, this disease should be listed as differential diagnosis for liver tumor with clinically benign characteristics.

A case of IgG4-related lymphadenopathy, pericarditis, coronary artery periarteritis and luminal stenosis

Immunoglobulin G4 (IgG4)-related disease is an emerging new clinicopathological disorder that is characterized by elevation of serum IgG4 levels and histological findings of IgG4-positive plasmacytic infiltration. IgG4-related disease may appear synchronously or metachronously in a wide variety of organs. The current patient was found to have pericardial effusion and retroperitoneal fibrosis. He was subsequently diagnosed with coronary artery stenosis. 18F-FDG positron emission tomography showed enhanced FDG uptake in lymph nodes as well as pericardial and peri-aortic tissue. Histopathology of the mediastinal lymph node showed the infiltration of numerous IgG4-positive cells, leading to the diagnosis of IgG4-related lymphadenopathy with pericardial and periarterial involvement.

Surgical treatment for abdominal actinomycosis: A report of two cases

Since actinomycosis sometimes causes an abdominal tumor which mimics malignancy, treatment strategy varies from case to case. We herein report two cases which were treated with a combination of antibiotics and surgical intervention. Both patients presented with an intra-abdominal tumor lesion mimicking malignant disease after an appendectomy for acute appendicitis. Case 1 received surgical extirpation of the abdominal tumor in the liver and kidney twice since the clinical diagnosis of actinomycosis was not made. In contrast, case 2 was successfully treated by a combination of antibiotics and laparoscopic surgery following the experience of case 1. When a high probability diagnosis can be made, a laparoscopic approach is a useful and effective option to treat this condition.

Focal hepatic steatosis surrounding a metastatic insulinoma

Reported herein is a case of focal hepatic steatosis surrounding a metastatic insulinoma in the liver of a 69‐year‐old woman. The patient complained of losing consciousness after meals, and hypoglycemia and hyperinsulinemia were confirmed. On CT and abdominal angiography a mass, 1 cm in diameter, was seen in the tail of the pancreas. In the early phase of dynamic CT a mass, 5 mm in diameter, was seen in the liver. In the late phase this mass appeared to be 3 cm in diameter. An arterial calcium stimulation/venous sampling test showed insulin levels after calcium injections in the hepatic artery to be extremely high. Thus, the liver tumor was diagnosed as a metastatic insulinoma, and distal pancreatectomy and partial resection of the liver were performed. The pancreatic tumor cells were immunohistochemically positive for insulin. The liver tumor was pale yellow. A white area surrounded the tumor. Histologically, the liver tumor was an insulinoma and the white area was focal fatty change of the liver. High insulin levels are said to inhibit oxidation of free fatty acids into triglycerides, causing free fatty acids to accumulate in hepatocytes. Focal hepatic steatosis caused by the local effects of insulin can present as a focal rim surrounding a metastatic insulinoma.